التفاصيل البيبلوغرافية
| العنوان: |
Clinical Characteristics and Long-term Follow-up of Patients with Diabetes Due To PTF1A Enhancer Mutations. |
| المؤلفون: |
Demirbilek, Huseyin, Cayir, Atilla, Flanagan, Sarah E., Yıldırım, Ruken, Kor, Yılmaz, Gurbuz, Fatih, Haliloğlu, Belma, Yıldız, Melek, Baran, Rıza Taner, Akbas, Emine Demet, Demiral, Meliha, Ünal, Edip, Arslan, Gulcin, Vuralli, Dogus, Buyukyilmaz, Gonul, Al-Khawaga, Sara, Saeed, Amira, Maadheed, Maryam Al, Khalifa, Amel, Onal, Hasan |
| المصدر: |
Journal of Clinical Endocrinology & Metabolism; Dec2020, Vol. 105 Issue 12, p1-9, 9p |
| مصطلحات موضوعية: |
PEOPLE with diabetes, PITUITARY dwarfism, FERRITIN, GENE enhancers, FETAL growth retardation, PANCREAS, RESEARCH, GENETICS, CHOLESTASIS, GENETIC mutation, NEONATAL diseases, RESEARCH methodology, DIABETES, EXOCRINE pancreatic insufficiency, MEDICAL cooperation, EVALUATION research, SELF-report inventories, COMPARATIVE studies, SYMPTOMS, RESEARCH funding, TRANSCRIPTION factors, GENETIC techniques, LONGITUDINAL method, DISEASE complications |
| مستخلص: |
Context: Biallelic mutations in the PTF1A enhancer are the commonest cause of isolated pancreatic agenesis. These patients do not have severe neurological features associated with loss-of-function PTF1A mutations. Their clinical phenotype and disease progression have not been well characterized.Objective: To evaluate phenotype and genotype characteristics and long-term follow-up of patients with PTF1A enhancer mutations.Setting: Twelve tertiary pediatric endocrine referral centers.Patients: Thirty patients with diabetes caused by PTF1A enhancer mutations. Median follow-up duration was 4 years.Main Outcome Measures: Presenting and follow-up clinical (birthweight, gestational age, symptoms, auxology) and biochemical (pancreatic endocrine and exocrine functions, liver function, glycated hemoglobin) characteristics, pancreas imaging, and genetic analysis.Results: Five different homozygous mutations affecting conserved nucleotides in the PTF1A distal enhancer were identified. The commonest was the Chr10:g.23508437A>G mutation (n = 18). Two patients were homozygous for the novel Chr10:g.23508336A>G mutation. Birthweight was often low (median SDS = -3.4). The majority of patients presented with diabetes soon after birth (median age of diagnosis: 5 days). Only 2/30 presented after 6 months of age. All patients had exocrine pancreatic insufficiency. Five had developmental delay (4 mild) on long-term follow-up. Previously undescribed common features in our cohort were transiently elevated ferritin level (n = 12/12 tested), anemia (19/25), and cholestasis (14/24). Postnatal growth was impaired (median height SDS: -2.35, median BMI SDS: -0.52 SDS) with 20/29 (69%) cases having growth retardation.Conclusion: We report the largest series of patients with diabetes caused by PTF1A enhancer mutations. Our results expand the disease phenotype, identifying recurrent extrapancreatic features which likely reflect long-term intestinal malabsorption. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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